Patients with non-insulin dependent diabetes mellitus (NIDDM) show insulin resistance and impaired glucose tolerance. They have also been shown to have parasympathetic neuropathies. Patients with chronic liver disease also show insulin resistance.
Currently, there is no suitable treatment for insulin resistance other than diet, exercise or weight loss which are of minimal use in liver disease and variable use in diabetes.
The present inventors developed an animal model of insulin resistance produced by nerve damage, and were able to produce insulin resistance in cats by surgical interruption of the mixed nerve bundle to the liver (Xie et al. (1993)).
They further demonstrated that the same degree of resistance could be produced by pharmacological blockade of parasympathetic nerve function using the muscarinic receptor antagonist, atropine (Xie et al., (1994), Proc. West. Pharmacol. Soc., v. 37, pp. 39-40).
Using a new animal model in the rat, the present inventors have devised a convenient method for screening compounds with therapeutic potential for treating insulin resistance. Using this screening system, the inventors have identified compounds which reduce or reverse insulin resistance.